DE102007004991B4 - Use of RiV preparations for the treatment of cerebral infarction - Google Patents
Use of RiV preparations for the treatment of cerebral infarction Download PDFInfo
- Publication number
- DE102007004991B4 DE102007004991B4 DE102007004991.0A DE102007004991A DE102007004991B4 DE 102007004991 B4 DE102007004991 B4 DE 102007004991B4 DE 102007004991 A DE102007004991 A DE 102007004991A DE 102007004991 B4 DE102007004991 B4 DE 102007004991B4
- Authority
- DE
- Germany
- Prior art keywords
- riv
- particles
- treatment
- cerebral infarction
- preparations
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 238000011282 treatment Methods 0.000 title claims abstract description 13
- 206010008118 cerebral infarction Diseases 0.000 title claims abstract description 11
- 208000026106 cerebrovascular disease Diseases 0.000 title claims abstract description 11
- 239000002245 particle Substances 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 6
- 238000005199 ultracentrifugation Methods 0.000 claims abstract description 5
- 238000000926 separation method Methods 0.000 claims abstract description 4
- 239000002904 solvent Substances 0.000 claims abstract description 4
- 239000008346 aqueous phase Substances 0.000 claims abstract description 3
- 238000000464 low-speed centrifugation Methods 0.000 claims abstract description 3
- 239000013049 sediment Substances 0.000 claims abstract description 3
- 210000002966 serum Anatomy 0.000 claims abstract description 3
- 230000037352 starvation stress Effects 0.000 claims abstract description 3
- 238000000108 ultra-filtration Methods 0.000 claims abstract description 3
- 238000001042 affinity chromatography Methods 0.000 claims abstract 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 claims description 3
- 238000011084 recovery Methods 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 208000006011 Stroke Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 5
- 241000700605 Viruses Species 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 3
- 229960001138 acetylsalicylic acid Drugs 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000036651 mood Effects 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 206010059282 Metastases to central nervous system Diseases 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 206010053648 Vascular occlusion Diseases 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- JFRJCQJVFMHZOO-QZHHGCDDSA-N n-(2-aminoethyl)-2-[4-[[2-[4-[[9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-6-yl]amino]phenyl]acetyl]amino]phenyl]acetamide Chemical compound C1=CC(CC(=O)NCCN)=CC=C1NC(=O)CC(C=C1)=CC=C1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 JFRJCQJVFMHZOO-QZHHGCDDSA-N 0.000 description 2
- 230000007971 neurological deficit Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 1
- 241000086254 Arnica montana Species 0.000 description 1
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 241001465356 Atropa belladonna Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 206010012455 Dermatitis exfoliative Diseases 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- 206010021639 Incontinence Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 240000001090 Papaver somniferum Species 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 244000107975 Strychnos nux-vomica Species 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 238000005282 brightening Methods 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000001627 cerebral artery Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 230000001632 homeopathic effect Effects 0.000 description 1
- 238000002169 hydrotherapy Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 230000036997 mental performance Effects 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- 235000006502 papoula Nutrition 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000036314 physical performance Effects 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 238000009160 phytotherapy Methods 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 208000027765 speech disease Diseases 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000003478 temporal lobe Anatomy 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 208000021331 vascular occlusion disease Diseases 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Vascular Medicine (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Zoology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Verwendung von BK-RiV-Präparaten, enthaltend RiV-Partikel mit einer Größe von 30 bis 70 nm zur Herstellung von Arzneimitteln zur Behandlung des Hirninfarktes, wobei die Herstellung der BK-RiV-Präparate folgende Schritte aufweist:- Kultivierung von primären, diploiden oder unbegrenzt wachsenden Vertebratenzellen;- Stressung der Zellen, bevorzugt mittels Hungerstress aufgrund der Verwendung von Medium ohne Serum, wodurch die 30-70 nm großen RiV-Partikel entstehen;- Zellaufschluss;- Abtrennung größerer Zelltrümmer;- Anreicherung der RiV-Partikel im resuspendierten Sediment durch Ultrazentrifugation und kurzzeitige Lösungsmittelbehandlung oder durch Ultrafiltration oder durch Affinitätschromatographie;- Gewinnung der wäßrigen, die RiV-Partikel enthaltenden Phase nach niedertouriger Zentrifugation.Use of BK-RiV preparations containing RiV particles with a size of 30 to 70 nm for the preparation of medicaments for the treatment of cerebral infarction, wherein the production of BK-RiV preparations comprises the following steps: - Cultivation of primary, diploid or unlimited - stressing the cells, preferably by starvation stress due to the use of medium without serum, resulting in the 30-70 nm RiV particles, - cell disruption, - separation of larger cell debris, - enrichment of the RiV particles in the resuspended sediment by ultracentrifugation and short-term solvent treatment or by ultrafiltration or by affinity chromatography, - recovery of the aqueous phase containing the RiV particles after low-speed centrifugation.
Description
Die Erfindung betrifft die Verwendung eines Präparates, das aus BK-RiV (Bio-komplex-Reaktionsmuster in Vertebratenzellen) besteht, im wesentlichen repräsentiert durch 30 bis 70 nm (im Mittel 50 nm) große sphärische RiV-Partikel, zur Nachsorge des Hirninfarktes und anderer Erkrankungen, die mit akuten Durchblutungsstörungen verbunden sind und bei denen bisher bekannte Arzneimittel nicht ausreichend wirken oder/und mit stärkeren Nebenwirkungen verbunden sind.The invention relates to the use of a preparation consisting of BK-RiV (bio-complex reaction patterns in vertebrate cells), substantially represented by 30 to 70 nm (average 50 nm) spherical RiV particles, for the follow-up of cerebral infarction and others Diseases that are associated with acute circulatory disorders and in which previously known drugs are not sufficient or / and are associated with more severe side effects.
Dem Hirninfarkt liegt eine akute Durchblutungsstörung des Gehirns zugrunde, die „schlagartig“ unterschiedlichste Funktionsstörungen und vielfach auch Funktionsverluste zur Folge hat. Auslöser für einen ischämischen Insult ist entweder ein Gefäßverschluss (arterielle Thrombose) aufgrund einer Arteriosklerose oder ein von der Halsschlagader oder vom Herzen ausgehendes, losgelöstes und in die Gehirnarterien gelangtes Blutgerinnsel (Embolie). Wenn es nicht gelingt, den Sauerstoffmangel rasch zu beheben, stirbt das nicht mehr durchblutete Hirngewebe nach einigen Stunden ab. Die Folgeschäden sind sehr unterschiedlich, je nachdem welche Hirnanteile betroffen sind. Ist beispielsweise das Sprachzentrum betroffen, sind Sprachstörungen die Folge („Schlaganfall“ in: Praxisatlas Gesundheit; Wissen Media Verlag GmbH u ADAC Verlag GmbH München 2002). Der Schlaganfall ist in den Industrieländern die dritthäufigste Todesursache. Ca. ein Drittel der Patienten bleibt auf lange Sicht pflegebedürftig und schwer behindert. Etwa 80 % der Schlaganfälle sind auf eine mangelhafte Durchblutung des Gehirns zurückzuführen. Die Diagnose - ob Hirninfarkt oder Hirnblutung - wird heute durch bildgebende Verfahren wie Computertomographie (CT) oder Kernspintomographie (Magnetresonanztomographie (MRT) gestellt.Cerebral infarction is based on an acute circulatory disorder of the brain, which "suddenly" has a variety of dysfunctions and often also loss of function. The trigger for an ischemic insult is either a vascular occlusion (arterial thrombosis) due to arteriosclerosis or a blood clot (embolism) released from the carotid artery or from the heart and released into the cerebral arteries. If it fails to remedy the lack of oxygen quickly, dies the no longer perfused brain tissue after a few hours. The sequelae are very different, depending on which brain parts are affected. If, for example, the language center is affected, speech disorders are the consequence ("stroke" in: Praxisatlas Gesundheit, Wissen Media Verlag GmbH and ADAC Verlag GmbH Munich 2002). Stroke is the third leading cause of death in industrialized countries. Approximately One third of patients remain dependent on long-term care and are severely handicapped. About 80% of strokes are due to poor circulation in the brain. The diagnosis - whether cerebral infarction or cerebral haemorrhage - is made today by imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI).
Entsprechend dem Stand der Technik kann beim Hirninfarkt in den ersten sechs Stunden nach Beginn der Symptome intravenös ein Gerinnsel auflösendes Medikament (Thrombolyse mittels Gewebeplasminogenaktivator) verabreicht werden. Auch der Einsatz von Kalziumantagonisten unterstützt die Rückbildung der neurologischen Ausfälle, sofern sie innerhalb der ersten zwölf Stunden verabreicht werden („Schlaganfall“ in: Praxisatlas Gesundheit; Wissen Media Verlag GmbH u ADAC Verlag GmbH München 2002).According to the prior art, in the case of cerebral infarction, a clot-dissolving drug (thrombolysis by tissue plasminogen activator) may be intravenously administered in the first six hours after the onset of the symptoms. The use of calcium antagonists also supports the regression of neurological deficits, provided that they are administered within the first twelve hours ("Stroke" in: Praxisatlas Gesundheit, Wissen Media Verlag GmbH and ADAC Verlag GmbH Munich 2002).
Innerhalb der ersten 3 Stunden nach Einsetzen der Beschwerden können Verschlüsse der außerhalb des Gehirns gelegenen Arterien, also der Halsschlagader und ihrer Verzweigungen auch operativ wieder rückgangig gemacht werden. Weitere Maßnahmen beinhalten eine Unterstützung von Herz und Kreislauf, Atmung und insbesondere die Sauerstoffversorgung des Gehirns. Zur Vorbeugung einer Thrombose wird eine Heparintherapie eingeleitet.Within the first 3 hours after the onset of the symptoms, occlusions of the arteries outside the brain, ie the carotid artery and its branches, can also be reversed surgically. Other measures include support for the heart and circulation, breathing and especially the oxygenation of the brain. To prevent thrombosis heparin therapy is initiated.
In der Nachsorge stellt die Therapie mit Acetylsalicylsaure (ASS) einen wirksamen medikamentösen Schutz vor einem erneuten Schlaganfall dar. Sie verhindert, dass sich Gerinnsel bilden und erneut ein Gefäß verschließt. Teurere Thrombozytenaggregationshemmer mit dem gleichen Effekt haben aber im Vergleich zum ASS nicht die Nebenwirkungen auf die Magenschleimhaut. Die Rehabilitation des Schlaganfallpatienten soll möglichst noch im Krankenhaus beginnen, wobei Krankengymnastik, Arbeitstherapie und Sprachübungen helfen sollen, die neurologischen Ausfälle zu reduzieren oder besser zu kompensieren (Praxisatlas Gesundheit, S. 415). Trink- und Essschwierigkeiten, Inkontinenz, verstärkt durch die Bewegungsstörungen und Druckstellen gehören oft zu den alltäglichen Problemen, die häufig Depressionen nach sich ziehen.In the follow-up therapy with acetylsalicylic acid (ASA) is an effective medical protection against a new stroke. It prevents clots from forming and closing a vessel again. More expensive platelet aggregation inhibitors with the same effect, however, do not have the side effects on the gastric mucosa compared to the ASA. The rehabilitation of the stroke patient should start in the hospital if possible, whereby physiotherapy, work therapy and language exercises should help to reduce the neurological deficits or better compensate (Praxisatlas Gesundheit, p. 415). Drinking and eating difficulties, incontinence, aggravated by movement disorders and pressure points are often among the everyday problems that often cause depression.
Bei der komplementären Medizin seien neben homöopathischen Mitteln wie Arnica montana, Belladonna, Nux vomica, Schlafmohn je nach Krankheitsbild, Ozontherapie, Hydrotherapie und Reflexzonentherapie die Phytotherapie zur Linderung der Beschwerden und Funktionsstörungen nach einem Schlaganfall erwähnt.In complementary medicine, in addition to homeopathic remedies such as Arnica montana, Belladonna, Nux vomica, opium poppy depending on the clinical picture, ozone therapy, hydrotherapy and reflexology mentions phytotherapy to alleviate the symptoms and functional disorders after a stroke mentioned.
Dem Stand der Technik entspricht weiterhin der in bisherigen Patentschriften vorgeschlagene Einsatz von BK-RiV-Präparaten u. a. zur Therapie von bestimmten Virus-bedingten Erkrankungen, insbesondere AIDS, zur Bekämpfung von Tumorerkrankungen, bevorzugt in Kombination mit der Chemo- oder Radiotherapie, extremen Schmerzzuständen, solchen des rheumatischen Formenkreises inklusive schweren Formen der Psoriasis (
Die zellkulturbasierenden RiV-Präparate, hergestellt nach den Verfahren, die in
Die vorliegende Erfindung bezweckt, insbesondere die Nachsorge und Rehabilitation des Hirninfarktes und anderer Erkrankungen, die mit plötzlichen Durchblutungsstörungen verbunden sind, deutlich zu verbessern, d. h. insbesondere die Rehabilitation durch den Einsatz eines BK-RiV-Präparates im Vergleich zu bekannten medikamentösen Behandlungen wesentlich zu verbessern und zu beschleunigen.The present invention aims to significantly improve, in particular, the aftercare and rehabilitation of cerebral infarction and other diseases associated with sudden circulatory disorders, i. H. In particular, to significantly improve and accelerate the rehabilitation through the use of a BK-RiV preparation compared to known drug treatments.
Es wurde überraschend gefunden, dass eine primäre oder adjuvante Behandlung (Nachsorge) des Hirninfarktes mittels BK-RiV (RiV-Partikelpräparaten oder RiV-spezifische Komponenten enthaltenden Praparaten), hergestellt nach bereits vorgeschlagenen Verfahren, durchgeführt werden kann. Die Behandlung führt zu einer erstaunlich schnellen und sehr deutlichen Reduzierung bzw. Aufhebung der Beschwerden und Funktionsstörungen. Paraklinisch normalisierte sich das subjektive Befinden äußerst rasch. Die Lebensqualität des Patienten wird durch die deutliche Steigerung seiner körperlichen und geistigen Leistungsfähigkeit und der Stimmungslage wesentlich verbessert.It has surprisingly been found that a primary or adjuvant treatment (follow-up) of cerebral infarction can be carried out by means of BK-RiV (RiV particle preparations or preparations containing RiV-specific components) prepared according to previously proposed methods. The treatment leads to a surprisingly fast and very significant reduction or cancellation of the symptoms and dysfunctions. Paraclinically, the subjective state of health normalized very quickly. The quality of life of the patient is significantly improved by the significant increase in his physical and mental performance and mood.
Nebenwirkungen wurden im Behandlungszeitraum (ca. 6 Wochen, dann Weiterbehandlung wegen Nierenzellkarzinom und Hirnmetastasen über weitere 4 Monate) nicht beobachtet.Side effects were not observed in the treatment period (about 6 weeks, then follow-up treatment for renal cell carcinoma and brain metastases for a further 4 months).
Die Herstellung von BK-RiV- bzw. RiV-Partikelpräparaten wird im wesentlichen durch folgenden Ablauf beschrieben:The preparation of BK-RiV or RiV particle preparations is described essentially by the following procedure:
Kultivierung von primären, diploiden oder unbegrenzt wachsenden Vertebratenzellen, Stressung der Zellen zwecks Anreicherung von BK-RiV-spezifischen Komponenten, insbesondere der etwa 30-70 nm großen RiV-Partikel, vorzugsweise durch Hungerstress (Medium ohne Serum), nach Zellaufschluss mit oder ohne den serumfreien Zellkulturüberstand, Abtrennung größerer Zelltrümmer, Ultrazentrifugation und kurzzeitige Lösungsmittelbehandlung des resuspendierten Sediments, Gewinnung der wässrigen Phase nach niedertouriger Zentrifugation. Vorzugsweise folgt zuletzt ein Inaktivierungsschritt (10 min. 100°C im Wasserbad, siehe
Das RiV-Präparat wird vorzugsweise aus Zellen porcinen, bovinen oder humanen Ursprungs gewonnen.The RiV preparation is preferably obtained from cells of porcine, bovine or human origin.
BK-RiV wird intramuskulär appliziert. Ein mögliches Applikationsschema ist:BK-RiV is administered intramuscularly. One possible application scheme is:
Am ersten Tag 1-2 ml; am 2. Tag 2-3ml; am 7. Tag 3ml; nach einer weiteren Woche Wiederholung, dann jede Woche 2-3 ml oder 14-tägig 5 ml, insgesamt mindestens 20 ml entsprechend dem Heilungsverlauf.On the first day 1-2 ml; on the 2nd day 2-3ml; on the 7th day 3ml; after another week repetition, then every week 2-3 ml or 14-day 5 ml, a total of at least 20 ml according to the healing process.
Eine Überdosierung wurde bisher bei allen behandelten Patienten nicht festgestellt. Alle 2 Tage 3ml wurden von einem Patienten (kein Infarktpatient) auch gut vertragen.An overdose has not been found in all patients treated so far. Every 2 days 3ml were well tolerated by one patient (no infarct patient).
Die Behandlung mit RiV-Präparat kann über Monate und sogar Jahre ausgedehnt werden und kann auch prophylaktisch erfolgen.The treatment with RiV preparation can be extended over months and even years and can also be prophylactic.
Anwendungsbeispiel:Example of use:
Patient, männlich, 54 Jahre;
Diagnose: Schlaganfall (Hirninfarkt), außerdem niedrig differenziertes Nierenzellkarzinom mit Hirnmetastasen im linken Temporallappen, diesbezüglich austherapiert;
Erstbefund (10 Tage nach Hirninfarkt): stationärer Patient in sehr schlechtem Allgemeinzustand, völlig bewegungsunfähig, Sprache lallend, kathederisiert, starke Druckschmerzen im Kopf trotz analgetischer Therapie, depressive Stimmungslage.Patient, male, 54 years;
Diagnosis: Stroke (cerebral infarction), also low-grade renal cell carcinoma with brain metastases in the left temporal lobe, in this respect ausherapiert;
Initial finding (10 days after cerebral infarction): inpatient in very poor general condition, completely unable to move, speech lolling, catheterized, severe pressure pain in the head despite analgesic therapy, depressive mood.
RiV-Therapie:RiV therapy:
Nach intramuskulärer Applikation von 8 ml BK-RiV innerhalb von 7 Tagen, verteilt auf 2 bzw. 3 ml pro Injektion, Schmerzsymptomatik beseitigt, aufgehellte Stimmungslage, Sprache verständlich; nach Applikation von weiteren 3ml am 17. Tag: normaler Harnfluss, erste Bewegungsübungen, gezielte Konversation möglich; nach Applikation von weiteren 2ml BK-RiV am 30. Tag: Nahrungsaufnahme außerhalb des Bettes, normaler Appetit, Sprache ausdauernd, klar und verständlich, nur noch geringe Pflegeaufwendungen. Nach weiteren 2ml 14 Tage später: erhöhter Harndrang, erhebliche Wasserauslagerungen aus dem Körper, Patient nimmt wieder normale Proportionen an und fühlt sich sehr wohl. Patient wird aus der Klinik nach Hause entlassen.After intramuscular administration of 8 ml BK-RiV within 7 days, divided into 2 or 3 ml per injection, pain symptom cleared, brightened mood, speech understandable; after application of another 3ml on the 17th day: normal urine flow, first movement exercises, targeted conversation possible; after application of another 2ml BK-RiV on the 30th day: food intake outside the bed, normal appetite, persistent language, clear and understandable, only minor care expenses. After a further 2 ml 14 days later: increased urination, significant water removal from the body, patient returns to normal proportions and feels very well. Patient is discharged from the clinic home.
Das hier eingesetzte RiV-Partikelpräparat (Versuchscharge aus Kalbernierenzellkulturen) hatte eine chemisch-colorimetrisch bestimmte Proteinkonzentration von 87 ± 91 µg/ml.The RiV particle preparation used here (test lot from calf kidney cell cultures) had a chemical colorimetrically determined protein concentration of 87 ± 91 μg / ml.
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102007004991.0A DE102007004991B4 (en) | 2006-08-14 | 2007-02-01 | Use of RiV preparations for the treatment of cerebral infarction |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102006038016 | 2006-08-14 | ||
DE102006038016.9 | 2006-08-14 | ||
DE102007004991.0A DE102007004991B4 (en) | 2006-08-14 | 2007-02-01 | Use of RiV preparations for the treatment of cerebral infarction |
Publications (2)
Publication Number | Publication Date |
---|---|
DE102007004991A1 DE102007004991A1 (en) | 2008-02-21 |
DE102007004991B4 true DE102007004991B4 (en) | 2018-08-30 |
Family
ID=38954999
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE102007004991.0A Active DE102007004991B4 (en) | 2006-08-14 | 2007-02-01 | Use of RiV preparations for the treatment of cerebral infarction |
Country Status (1)
Country | Link |
---|---|
DE (1) | DE102007004991B4 (en) |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DD283330A5 (en) | 1984-12-27 | 1990-10-10 | Adl Der Ddr,Friedrich-Loeffler-Institut Fuer Tierseuchen,Dd | ZEPARETH MANUFACTURING PROCESS FROM SELECTED CELL LINES LIMITED FINISHING POTENTIAL (FINIT LINES) |
DE19728323A1 (en) | 1997-06-27 | 1999-01-07 | Solisch Peter Dr Med Habil | Use of BK-RiV preparations and / or their components in medicine and veterinary medicine for diagnosis, therapy and prophylaxis, for testing and normalizing the "General Cellular Secretory Defense System" (AZSA) and the causally linked body conditions |
DE10017250A1 (en) | 2000-04-06 | 2001-10-11 | Peter Solisch | Preparing RiV-optimized vaccines and blood products, useful in human and veterinary medicine, giving products that contain RiV particles or anti-RiV antibodies |
WO2002067954A2 (en) | 2001-02-24 | 2002-09-06 | Varicula Gmbh | Use of particulate biocomplex bk-riv for producing a medicament for protecting and reconstructing the hepatic parenchyma |
DE60016178T2 (en) | 1999-02-26 | 2005-12-01 | Synx Pharma Inc., Toronto | METHOD FOR DIAGNOSIS AND CHARACTERIZATION OF STROKE |
DE102004036079A1 (en) | 2004-07-24 | 2006-02-09 | Liebermann, Herbert, Dr. | Preparation of cell culture based reaction pattern in vertebrate cell (RiV)-specific medicament, for e.g. treating tumor, HIV-infection, psoriasis and rheumatic diseases, comprises strongly heating RiV-preparation for ten minutes |
DE102006023560A1 (en) | 2006-05-19 | 2007-11-22 | Schabl, Christian, Dr. med. | Use of biocomplex-reaction pattern in vertebrate cells preparation e.g. primary therapy for idiopathic pulmonary fibrosis and as adjuvant therapy for cytostatics, for steroidal and non-steroidal anti-inflammatory drugs |
-
2007
- 2007-02-01 DE DE102007004991.0A patent/DE102007004991B4/en active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DD283330A5 (en) | 1984-12-27 | 1990-10-10 | Adl Der Ddr,Friedrich-Loeffler-Institut Fuer Tierseuchen,Dd | ZEPARETH MANUFACTURING PROCESS FROM SELECTED CELL LINES LIMITED FINISHING POTENTIAL (FINIT LINES) |
DE19728323A1 (en) | 1997-06-27 | 1999-01-07 | Solisch Peter Dr Med Habil | Use of BK-RiV preparations and / or their components in medicine and veterinary medicine for diagnosis, therapy and prophylaxis, for testing and normalizing the "General Cellular Secretory Defense System" (AZSA) and the causally linked body conditions |
DE60016178T2 (en) | 1999-02-26 | 2005-12-01 | Synx Pharma Inc., Toronto | METHOD FOR DIAGNOSIS AND CHARACTERIZATION OF STROKE |
DE10017250A1 (en) | 2000-04-06 | 2001-10-11 | Peter Solisch | Preparing RiV-optimized vaccines and blood products, useful in human and veterinary medicine, giving products that contain RiV particles or anti-RiV antibodies |
WO2002067954A2 (en) | 2001-02-24 | 2002-09-06 | Varicula Gmbh | Use of particulate biocomplex bk-riv for producing a medicament for protecting and reconstructing the hepatic parenchyma |
DE102004036079A1 (en) | 2004-07-24 | 2006-02-09 | Liebermann, Herbert, Dr. | Preparation of cell culture based reaction pattern in vertebrate cell (RiV)-specific medicament, for e.g. treating tumor, HIV-infection, psoriasis and rheumatic diseases, comprises strongly heating RiV-preparation for ten minutes |
DE102006023560A1 (en) | 2006-05-19 | 2007-11-22 | Schabl, Christian, Dr. med. | Use of biocomplex-reaction pattern in vertebrate cells preparation e.g. primary therapy for idiopathic pulmonary fibrosis and as adjuvant therapy for cytostatics, for steroidal and non-steroidal anti-inflammatory drugs |
Also Published As
Publication number | Publication date |
---|---|
DE102007004991A1 (en) | 2008-02-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5712207B2 (en) | Compositions and methods for prevention and treatment of brain diseases and conditions | |
US10537540B2 (en) | Pharmaceutical composition for promoting nerve injury restoration and application thereof | |
DE69024053T2 (en) | TREATMENT TO REDUCE EDM AND MUSCLE DAMAGE. | |
CN113413461A (en) | Medicine for resisting senile dementia and its preparing method | |
Gieler et al. | Delusional parasitosis as ‘folie à trois’ | |
JP5856725B2 (en) | Pharmaceutical composition for treating or preventing depression | |
Rafal et al. | Limb dystonia in progressive supranuclear palsy | |
TW201827044A (en) | Compositions for use in treating inflammatory bowel diseases | |
JP2023145593A (en) | Sarcodia ceylanica extract and use thereof | |
DE102007004991B4 (en) | Use of RiV preparations for the treatment of cerebral infarction | |
CN108938694A (en) | A kind of preparation method and applications of rhizome of chuanxiong ice spray | |
CN113116992A (en) | Composition for treating senile dementia | |
Neubauer et al. | Treatment of late neurologic sequelae of carbon monoxide poisoning with hyperbaric oxygenation: a case series | |
CN104399060A (en) | Application of metallothionein composite preparation in preparation of drugs for acupoint intervened treatment of cerebral apoplexy sequelae | |
US4552865A (en) | Psychotropic drugs | |
RU2208443C2 (en) | Method for treating multiple sclerosis | |
RU2233665C2 (en) | Agent for treatment of infantile spinal paralysis | |
CN114617865A (en) | Application of acetyl L-carnitine in preparing medicine for preventing or treating venous outflow obstruction diseases | |
WO2023273626A1 (en) | Composition for treating alzheimer's disease and preparation method therefor | |
RU2139061C1 (en) | Method of treating discirculatory encephalopathy | |
Ayache et al. | Methylphenidate in a patient with depression and respiratory insufficiency | |
DE1808173A1 (en) | Calcium orotate preparations for therapeu- - tic use | |
Mamidi et al. | Ayurvedic Management of Unilateral Decompressive Craniectomy and Cranioplasty Sequelae-A Case Report | |
RU2564905C1 (en) | Method of treating patients with localised scleroderma | |
RU2350331C1 (en) | Method of treatment of neurosis of obsessional conditions |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
8122 | Nonbinding interest in granting licences declared | ||
8120 | Willingness to grant licences paragraph 23 | ||
R081 | Change of applicant/patentee |
Owner name: VARICULA BIOTEC GMBH, DE Free format text: FORMER OWNERS: LIEBERMANN, HERBERT, DR., 17498 NEUENKIRCHEN, DE; MUELLER, HENRY, DR., 10999 BERLIN, DE Effective date: 20140127 Owner name: VARICULA BIOTEC GMBH, DE Free format text: FORMER OWNER: HERBERT LIEBERMANN,HENRY MUELLER, , DE Effective date: 20140127 |
|
R073 | Re-establishment requested | ||
R012 | Request for examination validly filed | ||
R005 | Application deemed withdrawn due to failure to request examination |
Effective date: 20140204 |
|
R074 | Re-establishment allowed | ||
R012 | Request for examination validly filed |
Effective date: 20140428 |
|
R074 | Re-establishment allowed |
Effective date: 20140524 |
|
R016 | Response to examination communication | ||
R016 | Response to examination communication | ||
R016 | Response to examination communication | ||
R016 | Response to examination communication | ||
R018 | Grant decision by examination section/examining division | ||
R081 | Change of applicant/patentee |
Owner name: VARICULA BIOTEC GMBH, DE Free format text: FORMER OWNER: VARICULA BIOTEC GMBH, 17166 TETEROW, DE |
|
R082 | Change of representative |
Representative=s name: GULDE & PARTNER PATENT- UND RECHTSANWALTSKANZL, DE |
|
R020 | Patent grant now final |